title: The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus.
abstract: BACKGROUND
  Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases.
  
  
  OBJECTIVE
  To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi.
  
  
  METHODS
  A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi.
  
  
  METHODS
  The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT.
  
  
  CONCLUSIONS
  Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction.
  
  
  CONCLUSIONS
  TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Cost
authors.forename: Scott E
authors.initials: SE
authors.lastname: Delacroix
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Sleeper
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.forename: Brian F
authors.initials: BF
authors.lastname: Chapin
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.forename: Stephen
authors.initials: S
authors.lastname: Culp
authors.forename: E Jason
authors.initials: EJ
authors.lastname: Abel
authors.forename: James
authors.initials: J
authors.lastname: Brugarolas
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Raj
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009392:Nephrectomy; D018579:Patient Selection; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage; D011859:Radiography; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077210:Sunitinib; D013781:Texas; D017131:Thrombectomy; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000601:surgery
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000068258:Bevacizumab; D000077210:Sunitinib